Amgen Drug Meets Primary Endpoint - Analyst Blog

Amgen (AMGN) recently presented much-awaited results on Xgeva (denosumab) from a phase III study that was conducted in 1,432 men with castrate-resistant prostate cancer. Top-line results from the ‘147 study showed that Xgeva improved median bone metastasis-free survival by 4.2 months compared to placebo.

Additionally, Xgeva significantly improved time to first occurrence of bone metastases. However, overall survival (secondary endpoint) was similar in both treatment arms. Moreover, the occurrence of adverse events like hypocalcemia and osteonecrosis of the jaw (ONJ) was higher in the Xgeva arm.

Xgeva sales should receive a major boost if Amgen succeeds in gaining approval for the prevention of bone metastases in prostate and breast cancer patients. However, the lack of improvement in overall survival benefit could make it challenging for the company to gain approval for the expanded population.

Xgeva was approved by the US Food and Drug Administration (FDA) in Nov 2010 for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors.

Xgeva's approval was based on data from three pivotal phase III head-to-head studies that compared Xgeva to Novartis' (NVS) Zometa. Results indicated that Xgeva showed superiority over Zometa in reducing the risk of SREs in patients with breast or prostate cancer and bone metastases. Xgeva was also shown to delay the onset of bone complications compared to Zometa.

Prior to the presentation of data from study ‘147, Amgen presented new data on Xgeva from the pivotal phase III ‘136 study which compared Xgeva with Zometa. Longer-term data from the study supported Xgeva's superiority in delaying the time to first on-study skeleton-related event (SRE) compared to Zometa. While Xgeva delayed the time to first on-study SRE by 18%, the time to first-and-subsequent on-study event was delayed by 22%. 

Moreover, Amgen said that the median time to first on-study SRE was five months longer in the Xgeva arm compared to the Zometa arm (32.4 months versus 27.4 months) in patients with advanced breast cancer and bone metastases.

A higher incidence of osteonecrosis of the jaw was reported in the Xgeva arm compared to the Zometa arm (2.5% versus 1.8%). The additional data from the ‘136 trial should help Xgeva gain share from Zometa.

Denosumab is also available under the trade name Prolia for the treatment of osteoporosis in postmenopausal women at increased risk of fracture or patients who have failed or are intolerant to other osteoporosis treatments.

Amgen gained approval for Prolia in both the US and the EU in mid-2010. However, initial sales have been disappointing. Prolia sales for the recently reported third quarter of 2010 were $10 million, well below expectations. Prolia ramp up remained slow under the buy and bill environment.

While we believe that expanded reimbursement coverage will help drive sales, the Nov 2010 approval for the solid tumor population should provide a major boost to revenues.

Neutral on Amgen

We currently have a Neutral recommendation on Amgen, which is supported by a Zacks #3 Rank (short-term Hold rating). Amgen is in a challenging growth period given the slowdown in sales of key products like Aranesp due to several reasons like labels restricting usage and other safety related issues. Moreover, products like Enbrel are facing intense competition from new competitors.

With several of Amgen's key products slated to lose patent protection over the next few years, the company has a lot riding on the successful commercialization of Prolia/Xgeva. The Nov 2010 approval of Xgeva is a major boost for the company and should help drive revenues going forward. Amgen is currently seeking regulatory approval for Xgeva in tother territories.

 
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